Morpholine → 6-Chloro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

HRID 2045385Notes

Reaction equation

HRID 2045385 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([Cl:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1)[C:11]([CH3:23])([CH3:22])[CH2:10]2)=[O:4].[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([Cl:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:16]=1)[C:11]([CH3:23])([CH3:22])[CH2:10]2)=[O:4]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 674420582-(3-Bromo-phenyl)-6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

Product 1

HCID 674427946-Chloro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-(3-bromo-phenyl)-6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (5.6 g, 13.7 mmol), morpholine (12 mL, 137 mmol), copper(I) iodide (1.1 g, 5.4 mmol), N,N-dimethylglycine hydrochloride (1.5 g, 10.9 mmol) and potassium carbonate (5.7 g, 41.1 mmol) in dimethyl sulfoxide (35 mL) was stirred at 120° C. for 16 h. Then the reaction mixture cooled to room temperature. The reaction mixture was extracted with ethyl acetate (2×150 mL), washed with water (2×50 mL) and saturated aqueous ammonium chloride solution (2×50 mL), dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 6-chloro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (4.5 g, 80%) as a yellow solid which was used for next step without further purification: LC/MS m/e calcd for C23H27ClN2O3 (M+H)+: 415.94, observed: 415.1.

Workup

  1. temperatureThen the reaction mixture cooled to room temperature
  2. extractionThe reaction mixture was extracted with ethyl acetate (2×150 mL)
  3. washwashed with water (2×50 mL) and saturated aqueous ammonium chloride solution (2×50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-812a846960bb469fa4c776222e9ea865
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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